Synthetic Chemistry Core

该核心的总体目标是为该NCDDG的所有三个项目提供化学支持，以便在该拟议研究的第五年结束时，淋巴瘤靶向药物的临床候选药物将准备好进行临床试验。国家的最先进的组合库方法将被用来发现细胞表面结合肽，将证明在治疗和治愈难治性人类B细胞恶性肿瘤有用。该核心的主要目标是开发使用肽和拟肽化合物开发癌症靶向治疗所需的所有化学物质。该核心提供的具体服务如下：一珠一化合物组合文库的设计与合成，通过全细胞筛选分离的阳性化合物珠的微测序与解码，设计 和合成用于细胞粘附谱的化学微阵列，设计和合成各种配体-缀合物（荧光的、生物素化的、光-和化学-亲和标记的、以及DOTA-标记的配体、毒素-配体），以供所有3个程序用于体外或体内研究。对于DOTA标记的配体，将制备单价、二价和寡价形式以确定具有有利药代动力学参数的最佳形式。

The overall goal of this core is to provide chemical support for all the three programs of this NCDDG, so that clinical candidate for lymphoma targeting agents will be ready for clinical testing by the end of the fifth year of this proposed research. State-of-the-art combinatorial library methods will be used to discover cell surface binding peptides that will prove useful in the treatment and cure of refractory human B-cell malignancies. The main objective of this core is to develop all the chemistries needed for the development of targeted-therapy in cancers using peptide and peptidomimetic compounds. Specific services provided by this core are as follows: design and synthesis of one-bead one-compound combinatorial libraries, microsequencing and decoding of positive compound-beads isolated through whole-cell screening, design and synthesis of chemical microarrays for cell adhesion profiling, design and synthesis of various ligand-conjugates (fluorescent, biotinylated, photo- and chemo-affinity label, and DOTA-labled ligands, toxin-ligand) to be used by all 3 programs for either in vitro or in vivo studies. For the DOTA-labeled ligands, monovalent, bivalent, and oligovalent forms will be prepared for determination of the optimal form with favorable pharmacokinetic parameters.